CtBPs Sense Microenvironmental Oxygen Levels to Regulate Neural Stem Cell State

被引：16

作者：

Dias, Jose M. ^{[1
]}

Ilkhanizadeh, Shirin ^{[2
]}

Karaca, Esra ^{[2
]}

Duckworth, Joshua K. ^{[2
]}

Lundin, Vanessa ^{[1
]}

Rosenfeld, Michael G. ^{[3
]}

Ericson, Johan ^{[1
]}

Hermanson, Ola ^{[2
]}

Teixeira, Ana I. ^{[1
]}

机构：

[1] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden

[2] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden

[3] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA

来源：

CELL REPORTS | 2014年 / 8卷 / 03期

基金：

瑞典研究理事会;

关键词：

EXPRESSION; DIFFERENTIATION; NOTCH; LOCALIZATION; REPRESSOR; GROUCHO; GENES; ROLES; HES1;

D O I：

10.1016/j.celrep.2014.06.057

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Bone morphogenetic proteins (BMPs) secreted by the dorsal neural tube and overlying ectoderm are key signals for the specification of the roof plate and dorsal interneuron populations. However, the signals that confer nonneurogenic character to the roof plate region are largely unknown. We report that the roof plate region shows elevated oxygen levels compared to neurogenic regions of the neural tube. These high oxygen levels are required for the expression of the antineuronal transcription factor Hes1 in the roof plate region. The transcriptional corepressor CtBP is a critical mediator of the oxygen- sensing response. High oxygen promotes a decrease in the CtBP occupancy of the promoter of Hes1. Furthermore, under conditions of high oxygen and BMP, CtBP associates with HES1 and represses neurogenesis. We propose that CtBP integrates signals originating from microenvironmental levels of oxygen and BMP to confer nonneurogenic character to the roof plate region.

引用

页码：665 / 670

页数：6

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